59284

神经网络昆斯林的新闻组分类2006

100,000 Americans are affected by retinitis pigmentosus, a hereditary disease 
that causes blindness. In addition, each year more than 15,000 people undergo 
surgical procedures to repair retinal detachments and other retinal traumas. 
     The research was funded in part by the RP (Retinitis Pigmentosa) 
Foundation Fighting Blindness, Regeneron Pharmaceuticals and the National Eye 
Institute. It was conducted by Drs. Matthew M. LaVail, Kazuhiko Unoki, Douglas 
Yasurnura, Michael T. Matthes and Roy H. Steinberg at UCSF, arld Dr. C;eorge 
Yancoooulos, Regeneron's Vice President for Discovery. Regeneron holds an 
exclusive license for this research from UCSF.
     In the research described in the PNAS , a light-damage model was used to 
assess the survival-promoting activity of a number of naturally occurring 
substances. Experimental rats were exposed to constant light for one week. 
Eyes that had not been treated with an effective factor lost most of their 
photoreceptor cells -- the rods and cones of the retina -- after light 
exposure. Brain Derived Neurotrophic Factor (BDNF) and Ciliary Neurotrophic 
Factor (CNTF) were particularly effective in this model without causing 
unwanted side effects; other factors such as Nerve Growth Factor (NGF) and 
Insulin-like Growth Factor (IGF-1) were not effective in these experiments. 
     Discussing the research, Dr. Jesse M. Cedarbaum, Regeneron's Director of 
Clinical Research, said, "BDNF's ability to rescue neurons in the retina that 
have been damaged by light exposure may hold promise for the treatment of age-
related macular degeneration, one of the leading causes of vision impairment, 
and for retinal detachment. Following detachment, permanent vision loss may 

HICNet Medical Newsletter                                              Page 18
Volume  6, Number 11                                           April 25, 1993

result frorn the death of detached retinal cells. It is possible that BDNF 
could play a role in rescuing those cells once the retina has been reattached 
surgically." 
     "Retinitis pigmentosa is a slowly progressing disease that causes the 
retina to degenerate over a period of years or even decades. Vision decreases 
to a small tunnel of sight and can result in total blindness. It is our hope 
that research on growth factors will provide a means to slow the progression 
and preserve useful vision throughout life," stated Jeanette S. Felix, Ph.D., 
Director of Science for the RP Foundation Fighting Blindness. 
     In addition to the work described , Regeneron is developing BDNF in 
conjunction with Aingen Inc. [NASDAQ:AMGN] as a possible treatment for 
peripheral neuropathies associated with diabetes and cancer chemotherapy, 
motor neuron diseases, Parkinson's disease, and Alzheimer's disease. By 
itself, Regeneron is testing CNTF in patients with arnyotrophic lateral 
sclerosis (commonly known as Lou Gehrig's disease). 
     Regeneron Pharlnaceuticals, Inc., based in Tarrytown, New York, is a 
leader in the discovery and development of biotechnology-based compounds for 
the treatment of neurodegenerative diseases, peripheral neuropathies and nerve 
injuries, which affect more than seven million Americans. Drs. LaVail and 
Steinberg of UCSF are consultants to Regeneron.

























HICNet Medical Newsletter                                              Page 19
Volume  6, Number 11                                           April 25, 1993

                 Affluent Diet Increases Risk Of Heart Disease

                          Research Resources Reporter
                           written by Mary Weideman
                                 Nov/Dec 1992
                         National Institutes of Health


     High-fat, high-calorie diets rapidly increase risk factors for coronary 
heart disease in native populations of developing countries that have 
traditionally consumed diets low in fat.  These findings, according to 
investigators at the Oregon Health Sciences University in Portland, have 
serious implications for public health in both industrialized and developing 
countries. 
     "This study demonstrates why we can develop coronary heart disease and 
have higher blood cholesterol and triglyceride levels.  It shows also the 
importance of diet and particularly the potential of the diet to increase body 
weight, thereby leading to a whole host of other health problems in developing 
countries and affluent nations as well," explains principal investigator Dr. 
William E. Connor, head of the section of clinical nutrition and lipid 
metabolism at Oregon Health Sciences University. 
     Over the past 25 years Dr. Connor and his team have characterized the 
food and nutrient intakes of the Tara humara Indians in Mexico, while 
simultaneously documenting various aspects of Tarahumara lipid metabolism.  
These native Mexicans number approximately 50,000 and reside in the Sierra 
Madre Occidental Mountains in the state of Chihuahua.  The Tarahumaras have 
coupled an agrarian diet to endurance racing.  Probably as a result, coronary 
heart disease, which is so prevalent in Western industrialized nations, is 
virtually non existent in their culture.  Loosely translated, the name 
Tarahumara means "fleet of foot," reflecting a tribal passion for betting on 
"kickball" races, in which participants run distances of 100 miles or more 
while kicking a machete-carved wooden ball.
     The typical Tarahumara diet consists primarily of pinto beans, tortillas, 
and pinole, a drink made of ground roasted corn mixed with cold water, 
together with squash and gath ered fruits and vegetables.  The Tara humaras 
also eat small amounts of game, fish, and eggs.  Their food contains 
approximately 12 percent of total calories as fat of which the majority (69 
percent) is of vegetable origin.  Dietician Martha McMurry, a coinvestigator 
in the study, describes their diet as simple and very rich in nutrients while 
low in cholesterol and fat.
     The Tarahumaras have average plasma cholesterol levels of 121 mg/ dL, 
low-density lipoprotein (LDL)-cholesterol levels of 72 mg/dl, and high-density 
lipoprotein (HDL)-cholesterol levels of 32 to 42 mg/dl.  All of those values 
are in the good, low-risk range, according to the researchers.  Elevated 
cholesterol and LDL-cholesterol levels are considered risk factors for heart 

HICNet Medical Newsletter                                              Page 20
Volume  6, Number 11                                           April 25, 1993

disease.  HDL-cholesterol is considered beneficial.  In previous studies the 
Tarahumaras had been found to be at low risk for cardiac disease, although 
able to respond to high-cholesterol diets with elevations in total and LDL-
cholesterol. 
     Clinical Research Center dietitian McMurry and coinvestigator Maria 
Teresa Cerqueira established a metabolic unit in a Jesuit mission school 
building near a community hospital in the small village of Sisoguichi.  Food 
was weighed, cooked, and fed to the study participants under the 
investigators' direct supervision, ensuring that subjects ate only food 
stipulated by the research protocol.  Fasting blood was drawn twice weekly, 
and plasma samples were frozen and shipped to Dr. Connors laboratory for 
cholesterol, triglyceride, and lipoprotein analyses.  Regular measurements 
included participant body weight, height, and triceps skin fold thickness.  
Thirteen Tarahumaras, five women and eight men, including one adolescent, were 
fed their native diet for 1 week, followed by 5 weeks of an "affluent" diet. 
     "In this study we went up to a concentration of dietary fat that was 40 
percent of total calories.  This is the prototype of the holiday diet that 
many Americans consume a diet high in fat, sugar, and cholesterol, low in 
fiber," elaborates Dr. Conners. Such dietary characteristics are reflected in 
the cholesterol-saturation index, or CSI, recently devised research dietitian 
Sonja Conner working with Dr. Connor.  "The CSI is a single number that 
incorporates both the amount of cholesterol and the amount of saturated fat in 
the diet.  CSI indicates the diet's potential to elevate the cholesterol 
level, particularly the LDL," Dr. Connor explains.  The Tarahumaran diet 
averages a very low CSI of 20; Dr. Connor's "affluent" diet used in the study 
ranks a CSI of 149. 
     The experimental design of this study reflects the importance of 
establishing baseline plasma lipid levels, typical of the native diet, before 
exposing subjects to the experimental diet.  The standard curve relating 
dietary food intake to plasma cholesterol demonstrates a leveling off, or 
plateau, for consumption of large amounts of fat.  Changes in dietary fat 
and/or cholesterol in this range have little effect on plasma levels.  "You 
must have the baseline diet almost free of the variables you are going to put 
into the experimental diet.  The Framingham study, for example, did not 
discriminate on the basis of diet between individuals who got heart disease 
because the diet was already high in fat.  All subjects were already eating on 
a plateau," Dr. Connor says. 
     After 5 weeks of consuming the "affluent" diet, the subjects' mean plasma 
cholesterol levels had in creased by 31 percent, primarily in the LDL 
fraction, which rose 39 percent.  HDL-cholesterol increased by 31 per cent, 
and LDL to HDL ratios changed therefore very little.  Plasma triglyceride 
levels increased by 18 percent, and subjects averaged an 8-pound gain in 
weight.  According to Dr. Connor, lipid changes occurred surprisingly soon, 
yielding nearly the same results after 7 days of affluent diet as after 35 
days. 

HICNet Medical Newsletter                                              Page 21
Volume  6, Number 11                                           April 25, 1993

     The increase in HDL carries broad dietary implications for industrialized 
nations.  "We think HDL-cholesterol increased because we increased the amount 
of dietary fat over the fat content used in the previous Tarahumara metabolic 
study.  In that study we saw no change in HDL levels after raising the dietary 
cholesterol but keeping the fat relatively consistent with native consumption.  
In the present study we increased fat intake to 40 percent of the total 
calories.  We reached the conclusion in the Tarahumara study that HDL reflects 
the amount of dietary fat in general and not the amount of dietary 
cholesterol.  HDL must increase to help metabolize the fat, and it increased 
quite a bit in this study," Dr. Connor explains.
     Low HDL in the Tarahumarans is not typically an important predictor of 
coronary heart disease because they do not normally consume large amounts of 
fat or cholesterol.  HDL remains an important predictor to Americans because 
of their usual high fat intake. 
     Dr. Connor recommends a diet for Americans that contains less than 20 
percent of total calories as fat, less than 100 mg of cholesterol, and a CSI 
around 20, varying in accordance with caloric needs.  Such a diet is low in 
meat and dairy fat, high in fiber.  Dr. Connor also comments on recent 
suggestions that Americans adopt a "Mediterranean-style" diet.  "The original 
Mediterranean diet, in its pristine state, consisted of a very low intake of 
fat and very few animal and dairy products.  We are already eating a lot of 
meat and dairy products.  Simply to continue that pattern while switching to 
olive oil is not going to help the situation." 
     The World Health Organization (WHO) is focusing much attention on the 
emergence of diseases such as coronary heart disease in nations and societies 
undergoing technological development.  Dr. Connor says that coronary heart 
disease starts with a given society's elite, who typically eat a different 
diet than the average citizen.  "If the pattern of afluence increases, the 
entire population will have have a higher incidence of coronary heart disease, 
which places a termendous health care burden on a society.  WHO would like the 
developing countries to prevent coronary heart disease, so they can 
concentrate on other aspects of their economic development and on public 
health measures to improve general well-being, rather than paying for 
unnecessary, expensive medical technology," Dr. Connors says.
     "The overall implication of this study is that humans can readily move 
their plasma lipids and lipoprotein values into a high-risk range within a 
very short time by an affluent, excessive diet.  The present rate of coronary 
heart disease in the United States is 30 percent less than it was 20 years 
ago, so a lot has been accomplished.  We are changing rapidly," he concludes.






HICNet Medical Newsletter                                              Page 22
Volume  6, Number 11                                           April 25, 1993



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